Human Immunodeficiency Virus Type 1 (HIV-1) Infection
Conditions
Brief summary
Researchers are looking for new ways to treat HIV-1 (Human Immunodeficiency Virus Type 1). The usual (standard) treatment for HIV-1 is antiretroviral therapy (ART), which includes taking medicines to lower the amount of HIV-1 in the body. Standard ART helps people live longer, but people must take up to 3 medicines up to twice a day. Standard ART may also cause other health problems. Researchers want to know if a study ART works as well as a standard ART to treat HIV-1. The study ART combines 2 medicines, islatravir and ulonivirine, and is taken once a week. The goals of this study are to learn: 1) If the study ART works as well as a standard ART to treat HIV-1, and 2) About the safety of the study ART and if people tolerate it compared to a standard ART.
Interventions
DRUGISL
ISL 2 x 1 mg oral capsules administered qw for 96 weeks
DRUGULO
ULO 2 x 100 mg oral tablets administered qw for 96 weeks
DRUGBIC/FTC/TAF
BIC/FTC/TAF 50/200/25 mg oral tablet administered qd for 96 weeks
DRUGPlacebo for BIC/FTC/TAF
BIC/FTC/TAF-matching placebo oral tablet administered qd for 96 weeks
DRUGPlacebo to ISL/ULO
ISL/ULO-matching placebo oral tablets administered qw for 96 weeks
DRUGISL/ULO
ISL/ULO fixed-dose combination 2 mg/200 mg oral tablet administered qw for 96 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Phase 2: no masking Phase 3: Participant, Sponsor, and Investigator are masked
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Phase 2: Is human immunodeficiency virus type 1 (HIV-1) positive with Plasma HIV-1 ribonucleic acid (RNA) ≥500 and ≤100,000 copies/mL. * Phase 3: Is HIV-1 positive with Plasma HIV-1 RNA ≥500 copies/mL. * Phase 2: Has cluster of differentiation 4-positive (CD4+) T-cell count ≥200 cells/mm\^3. * Is naïve to antiretroviral therapy (ART), defined as having received no prior therapy with any antiretroviral agent following a diagnosis of HIV 1 infection.
Exclusion criteria
* Has human immunodeficiency virus type 2 (HIV-2) infection. * Has a diagnosis of an active acquired immune deficiency syndrome (AIDS)-defining opportunistic infection. * Has active hepatitis C virus (HCV) or active hepatitis B virus (HBV) infection. * Has a history of malignancy ≤5 years prior to providing documented informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or in situ anal cancer, or cutaneous Kaposi's sarcoma. * Has prior exposure to islatravir (ISL) or ulonivirine (ULO) for any duration any time prior to Day 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL at Week 24 | Week 24 | Plasma HIV-1 ribonucleic acid (RNA) quantification will be performed at the central laboratory using a polymerase chain reaction (PCR) assay. Percentage of participants with HIV-1 RNA \<50 copies/mL will be reported at week 24. |
| Phase 2: Percentage of Participants Who Experience an Adverse Event (AE) at Week 24 | Week 24 | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Phase 2: Percentage of Participants Who Discontinue Study Intervention Due to an AE at Week 24 | Week 24 | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Phase 3: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | Week 48 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA \<50 copies/mL will be reported at week 48. |
| Phase 3: Percentage of Participants Who Experience an AE at Week 48 | Week 48 | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Phase 3: Percentage of Participants Who Discontinue Study Intervention Due to an AE at Week 48 | Week 48 | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | Week 48 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA \<50 copies/mL will be reported at week 48. |
| Phase 2: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 | Week 96 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA \<50 copies/mL will be reported at week 96. |
| Phase 2: Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 24 | Week 24 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA \<200 copies/mL will be reported at week 24. |
| Phase 2: Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48 | Week 48 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA \<200 copies/mL will be reported at week 48. |
| Phase 2: Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96 | Week 96 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA \<200 copies/mL will be reported at week 96. |
| Phase 2: Mean Change From Baseline in Cluster of Differentiation 4-Positive (CD4+) T-Cell Count at Week 24 | Baseline (Day 1) and Week 24 | Blood samples will be collected to measure CD4+ T-cell count. The mean change from baseline in CD4+ T-cell count will be calculated at 24 weeks. |
| Phase 2: Mean Change From Baseline in CD4+ T-Cell Count at Week 48 | Baseline (Day 1) and Week 48 | Blood samples will be collected to measure CD4+ T-cell count. The mean change from baseline in CD4+ T-cell count will be calculated at 48 weeks. |
| Phase 2: Mean Change From Baseline in CD4+ T-Cell Count at Week 96 | Baseline (Day 1) and Week 96 | Blood samples will be collected to measure CD4+ T-cell count. The mean change from baseline in CD4+ T-cell count will be calculated at 96 weeks. |
| Phase 2: Percentage of Participants Who Experience an AE | Up to approximately 102 weeks | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Phase 2: Percentage of Participants Who Discontinue Study Intervention Due to an AE | Up to approximately 96 weeks | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Phase 2: Number of Participants With Evidence of Viral Drug Resistance-Associated Substitutions at Week 24 | Week 24 | Participants who meet the definition of clinically significant confirmed viremia (CSCV) or who discontinue study intervention for another reason and have HIV-1 RNA ≥200 copies/mL at the time of discontinuation, will be assessed for development of viral drug resistance. Among such participants, those with confirmed HIV-1 RNA ≥400 copies/mL will be included in the resistance analyses set. In addition, anyone for whom available genotypic and/or phenotypic data show evidence of resistance, irrespective of viral load, will also be included in the resistance analyses set. The number of participants in each treatment group who have evidence of resistance-associated substitutions at week 24 will be presented. |
| Phase 2: Number of Participants With Evidence of Viral Drug Resistance-Associated Substitutions at Week 48 | Week 48 | Participants who meet the definition of clinically significant confirmed viremia (CSCV) or who discontinue study intervention for another reason and have HIV-1 RNA ≥200 copies/mL at the time of discontinuation, will be assessed for development of viral drug resistance. Among such participants, those with confirmed HIV-1 RNA ≥400 copies/mL will be included in the resistance analyses set. In addition, anyone for whom available genotypic and/or phenotypic data show evidence of resistance, irrespective of viral load, will also be included in the resistance analyses set. The number of participants in each treatment group who have evidence of resistance-associated substitutions at week 48 will be presented. |
| Phase 2: Number of Participants With Evidence of Viral Drug Resistance-Associated Substitutions at Week 96 | Week 96 | Participants who meet the definition of clinically significant confirmed viremia (CSCV) or who discontinue study intervention for another reason and have HIV-1 RNA ≥200 copies/mL at the time of discontinuation, will be assessed for development of viral drug resistance. Among such participants, those with confirmed HIV-1 RNA ≥400 copies/mL will be included in the resistance analyses set. In addition, anyone for whom available genotypic and/or phenotypic data show evidence of resistance, irrespective of viral load, will also be included in the resistance analyses set. The number of participants in each treatment group who have evidence of resistance-associated substitutions at week 96 will be presented. |
| Phase 3: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 | Week 96 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA \<50 copies/mL will be reported at week 96. |
| Phase 3: Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48 | Week 48 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA \<200 copies/mL will be reported at week 48. |
| Phase 3: Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96 | Week 96 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay. Percentage of participants with HIV-1 RNA \<200 copies/mL will be reported at week 96. |
| Phase 3: Mean Change From Baseline in Cluster of Differentiation 4-Positive (CD4+) T-Cell Count at Week 48 | Baseline (Day 1) and Week 48 | Blood samples will be collected to measure CD4+ T-cell count. The mean change from baseline in CD4+ T-cell count will be calculated at 48 weeks. |
| Phase 3: Mean Change From Baseline in Cluster of Differentiation 4-Positive (CD4+) T-Cell Count at Week 96 | Baseline (Day 1) and Week 96 | Blood samples will be collected to measure CD4+ T-cell count. The mean change from baseline in CD4+ T-cell count will be calculated at 96 weeks. |
| Phase 3: Percentage of Participants Who Experience an AE | Up to approximately 102 weeks | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Phase 3: Percentage of Participants Who Discontinue Study Intervention Due to an AE | Up to approximately 96 weeks | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Phase 3: Number of Participants With Evidence of Viral Drug Resistance-Associated Substitutions at Week 48 | Week 48 | Participants who meet the definition of clinically significant confirmed viremia (CSCV) or who discontinue study intervention for another reason and have HIV-1 RNA ≥200 copies/mL at the time of discontinuation, will be assessed for development of viral drug resistance. Among such participants, those with confirmed HIV-1 RNA ≥400 copies/mL will be included in the resistance analyses set. In addition, anyone for whom available genotypic and/or phenotypic data show evidence of resistance, irrespective of viral load, will also be included in the resistance analyses set. The number of participants in each treatment group who have evidence of resistance-associated substitutions at week 48 will be presented. |
| Phase 3: Number of Participants With Evidence of Viral Drug Resistance-Associated Substitutions at Week 96 | Week 96 | Participants who meet the definition of clinically significant confirmed viremia (CSCV) or who discontinue study intervention for another reason and have HIV-1 RNA ≥200 copies/mL at the time of discontinuation, will be assessed for development of viral drug resistance. Among such participants, those with confirmed HIV-1 RNA ≥400 copies/mL will be included in the resistance analyses set. In addition, anyone for whom available genotypic and/or phenotypic data show evidence of resistance, irrespective of viral load, will also be included in the resistance analyses set. The number of participants in each treatment group who have evidence of resistance-associated substitutions at week 96 will be presented. |
| Phase 3: Mean Change From Baseline in Body Weight at Week 48 | Baseline (Day 1) and Week 48 | Body weight will be collected throughout the study. |
| Phase 3: Mean Change From Baseline in Body Weight at Week 96 | Baseline (Day 1) and Week 96 | Body weight will be collected throughout the study. |
Countries
Canada, France, Guatemala, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed